Drugs Acting on the Autonomic Nervous System

Drug

Bolus dose

Infusion rate

Phenylephrine

100 mcg

1 mcg/kg/min

Methoxamine

10 mg

Norepinephrine

16 mcg

0.1 mcg/kg/min

Epinephrine

8 mcg

0.05 mcg/kg/min

Metaraminol

5 mg

Ephedrine

10 mg

Mephentermine

30 mg

Dopamine

200 mcg

10 mcg/kg/min

Dobutamine

10 mcg/kg/min

Vasopressin

40 Units

0.6 Units/min

Sympatholytics

For both acute and chronic treatment of hypertension, beta-blockers have been a valuable clinical tool. The role of beta-blockers in anesthesia relates to both preanesthetic conditions and perioperative situations. In general, chronic beta-blocker therapy should be continued throughout the perioperative period. Perioperatively, abnormally high blood pressures can be treated with beta-blockers or with labetalol, an alpha- and beta-blocking agent. Both nonselective and selective beta-1-blocking agents can also be employed to lower high blood pressures. Esmolol is an ultrashort-acting beta-1 selective beta-blocker with an extremely short half-life of 9 min. Metoprolol, while selective, is longer acting than esmolol. The utility of metoprolol is for more sustained treatment of hypertension, such as when the patient has failed to take his or her daily beta-blocker. Other drugs, such as alpha-methyldopa, clonidine, and trimethaphan, no longer have practical clinical utility in controlling perioperative hypertension. Table 14.2 demonstrates several of the clinically useful beta-blocking agents in the prevention and treatment of perioperative hypertension. Included in the table are labetalol, a mixed alpha- and beta-blocker, and nitroprusside, a nitrovasodilator. Both these drugs are useful when conventional beta-blockade has not produced the desired reduction in blood pressure.

Table 14.2

Doses of commonly used sympatholytic agents for the perioperative period. These doses are intended for adult patients via an intravenous route. See text for details

Drug	Bolus dose	Infusion rate
Labetalol	5 mg	NA
Esmolol	30 mg	100 mcg/kg/min
Metoprolol	5 mg	100 mcg/kg/min
Nitroprusside	100 mcg	5 mcg/kg/min

Drug Interactions

Sympathomimetics

In general, serious drug interactions can arise when sympathomimetics are combined with agents that accentuate all or a portion of the actions of these adrenergic agonists. For example, classes of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) potentiate the sympathetic effects of adrenergic agonists by causing higher synaptic levels of the neurotransmitter norepinephrine. In some cases, this combination of sympathomimetic and MAOI can cause a fatal hypertensive crisis. In other drug combinations, only a part of the sympathetic action is seen. One of the side effects of the use of droperidol or haloperidol is a profound alpha-blockade. In combination with epinephrine, the effect of droperidol can be to cause further decreases in blood pressure: not only from the alpha-blockade but also from the unopposed beta-2 stimulation by epinephrine on the peripheral vasculature. When epinephrine is given to patients who are taking a nonselective beta-blocker, there can be an exaggerated increase in blood pressure due to unopposed alpha activity with no activation of beta-2 in the vasculature. Note that the nonselective beta–blocker can be the antiarrhythmic agent propranolol (taken orally) or the antiglaucoma medication timolol (given as eye drops). In both cases, there can be enough systemic absorption to cause these cardiovascular drug interactions. Sympathomimetic agents can also interact with volatile anesthetic agents to promote arrhythmias.

Sympatholytics

Drug interactions with sympatholytic agents can arise whenever there is an effect on the clinical action or the metabolism or excretion of the drug. Sympatholytic drugs tend to lower blood pressure and reduce contractility and they often have additive effects with other antihypertensive drugs and in clinical conditions such as congestive heart failure. Calcium channel blockers must be given cautiously to patients already on beta-blockers. Beta-blockers may decrease the effectiveness of oral hypoglycemic agents in the treatment of diabetes. Beta-blockers can reduce the effectiveness of theophylline in the treatment of asthma, as theophylline can reduce the effectiveness of beta-blockers in treating hypertension. Aspirin and NSAIDs can counteract the antihypertensive effects of beta-blockers, probably through their inhibition of prostaglandins. The combination of beta-blockers and MAO inhibitors can lead to increased blood pressure, through an unopposed beta-2 blockade in the resistance arterioles. Cold remedies that contain caffeine, pseudoephedrine, or ephedrine can counteract the effects of beta-blockers with their sympathomimetic effects.

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